PROJECT SUMMARY/ABSTRACT ? TRANSLATIONAL CORE We propose to establish a Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation at the University of Kentucky (UK). CPRI will serve as a comprehensive multidisciplinary center focused on translational chemical biology [the nexus of chemical biology (the application of chemical biology principles to develop validated probe/models to advance our understanding of biology) and pharmaceutical science (the application of pharmaceutical principles to advance leads/materials/devices that address unmet clinical needs)]. The COBRE will leverage and develop unique translational chemical biology research support infrastructure/expertise to facilitate junior faculty mentorship and career development, innovative biomedical research probe/tool/model/materials development and validation, and the early advancement of potential ?translatable? assets. Within this context, the CPRI Translational Core will provide key infrastructure and expertise to support experimental studies central to probe/lead/materials discovery. Under the co-direction of Drs. Markos Leggas and Jon Thorson, the Core will support assay design, development, validation and implementation; pilot screening campaigns; a suite of in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) assays; and first in animal ADMET/pharmacokinetics (PK) studies. Support in the Core will be tailored toward specific COBRE project/pilot needs and screening services will also leverage CPRI-exclusive compound collections (both natural products and synthetics). The Core?s services have been strategically designed to integrate with, and complement, the support provided by the CPRI Computational Core and the CPRI-affiliated COBRE for Molecular Medicine Organic Synthesis Core. Together, CPRI?s corresponding fully integrated research support capabilities and expertise will accelerate innovative, ?translatable? transdisciplinary research and facilitate junior investigator career development.